Association between HLA-A alleles and Alzheimer's disease in a southern Chinese community.
OBJECTIVE
HLA-A is a locus of the major histocompatibility complex situated on chromosome 6p21.3. Several genome-wide linkage analyses suggested that a putative locus predisposition for Alzheimer's disease (AD) is found on chromosome 6p21. In this study, we investigated the association between HLA-A alleles and AD in a Chinese community.


METHODS
Fine genotyping of 160 Chinese AD and 167 age-matched nondemented subjects was performed for the first time by sequence-based typing of the HLA-A locus.


RESULTS
We found that HLA-A2 carriers (including prevalent alleles, 0201, 0203 and 0207) were more prevalent in the AD group; the frequency of HLA-A2 was increased in AD patients versus controls, but the difference was not significant after Bonferroni correction for the number of alleles tested (p = 0.075). A gene-gene interaction was observed between ApoE and HLA-A, the presence of HLA-A24 (particularly the prevalent allele 2402) might act as another independent risk factor of developing AD for subjects not carrying the ApoE epsilon4 allele (relative risk = 2.98, 95% CI = 1.14-8.24). Carriers of HLA-A2 had an earlier onset of AD by 2.4 years (p = 0.030) and HLA-A2 interacted with ApoE epsilon4 in modulating the age at onset in AD.


CONCLUSIONS
This study suggested that HLA-A may be involved in the pathogenesis of AD.
Ma
Suk Ling
SL
Department of Chemical Pathology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
Tang
Nelson Leung Sang
NL
Tam
Cindy Woon Chi
CW
Lui
Victor Wing Cheong
VW
Suen
Eddie Wai Chui
EW
Chiu
Helen Fung Kum
HF
Lam
Linda Chiu Wa
LC
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004311:Double-Blind Method; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics*; D006579:Heterozygote; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D001057:Apolipoproteins E; D015234:HLA-A Antigens; D004247:DNA